USING FLP-RECOMBINASE TO CHARACTERIZE EXPANSION OF WNT1-EXPRESSING NEURAL PROGENITORS IN THE MOUSE

Here we demonstrate how a Flp recombinase-based tagging system can be used to link temporally distinct developmental events in the mouse. By directly following Flp-mediated DNA rearrangements we have analyzed t he adult expansion of embryonic neural progenitors which transiently e xpress the signaling factor Wnt1. We report Wnt1 promoter activity in embryonic cells that give rise to aspects of the adult midbrain, cereb ellum, spinal cord, and dorsal root ganglia. These findings show that cells transiently expressing Wnt1 play more than an inductive role dur ing early brain regionalization, giving rise to distinct adult brain r egions as well as neural crest derivatives. Moreover, these results re veal two new features of the Flp-FRT system: First, Flp(F70L) can effe ctively recombine target sites (FRTs) placed in an endogenous locus in a variety of tissues in vivo, despite previous in vitro evidence of t hermolability; and second, Flp(F70L) action can be predictably and tig htly regulated in the mouse embryo, making it suitable for fate mappin g applications. A further advantage of the Flp-FRT system is that mark ed lineages can ultimately be combined with germline mutations and def iciencies currently being generated using the Cre-loxP recombination s ystem - in this way it should be possible to analyze mutant gene activ ities directly for their effect on cell fate. (C) 1998 Academic Press.